Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation.

"all microbiome data (16s rrna amplicons) generated during the preparation of this study have been deposited in the ncbi sequence read archive with bioproject id prjna953087 . all metabolite data generated in the preparation of this study are available at 10 5281/zenodo 8015340. data availability data in this study have been presented where possible in aggregated form. all metabolite data generated in the preparation of this study are available at 10 5281/zenodo"

"Competing interests J. Magenau received consulting fees from INHIBRX. M.G. received consulting fees from Cabaletta Bio. C.A.L. received consulting fees from Astellas Pharmaceuticals, Odyssey Therapeutics and T-knife Therapeutics, and is an inventor on patents pertaining to KRAS-regulated metabolic pathways, redox control pathways in pancreatic cancer and targeting the GOT1 pathway as a therapeutic approach (US patent no. 2015126580-A1, 7 May 2015; US patent no. 20190136238, 9 May 2019; international patent no. WO2013177426-A2, 23 April 2015). All other authors declare no competing interests."

"We thank the volunteers who participated in the study and the clinical and research staff of the University of Michigan Bone Marrow Transplant program. This work was supported by the National Heart, Lung, and Blood Institute (grant no. P01 HL149633 to P.R., M.T. and M.M.R.), which facilitated all bio sample analyses. The funder had no role in the design and analysis of the study. RS was purchased using institutional startup funds (M.M.R.)."

"Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day −7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they were not (P < 0.0001). An exploratory objective was to evaluate plasma metabolites. We observed longitudinal changes in plasma metabolites compared to baseline, which were independent of RPS (P < 0.0001). However, in recipients of RPS, the dominant plasma metabolites were more stable compared to historical controls with significant difference at engraftment (P < 0.05). These results indicate that RPS in recipients of allogeneic HCT is feasible; in this study, it was associated with significant alterations in intestinal and plasma metabolites. A phase 2 trial examining the effect of RPS on graft-versus-host disease in recipients of allogeneic HCT is underway. ClinicalTrials.gov registration: NCT02763033. Data availability: Data in this study have been presented, where possible, in aggregated form. All metabolite data generated in the preparation of this study are available at 10.5281/zenodo.8015340. All microbiome data (16S rRNA amplicons) generated during the preparation of this study have been deposited in the NCBI Sequence Read Archive with BioProject ID PRJNA953087. This study was prospectively registered. The ClinicalTrials.gov registration is NCT02763033. The study is also under FDA IND application no. 132208. The ten patients from the pilot feasibility study presented in this study represent the initial part of a phase 2 randomized trial currently enrolling 60 additional patients to determine the clinical impact on acute GVHD."